To What End - Tracking and Assessing Community Engagement Across Universities

This is a presentation from the Coalition of Urban and Metropolitan Universities (CUMU) Conference in Omaha, Nebraska on October 12, 2015

Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration

Relating clinical symptoms to neuroanatomical profiles of brain damage and ultimately to tissue pathology is a key challenge in the field of neurodegenerative disease and particularly relevant to the heterogeneous disorders that comprise the frontotemporal lobar degeneration spectrum. Here we present a retrospective analysis of clinical, neuropsychological and neuroimaging (volumetric and voxel-based morphometric) features in a pathologically ascertained cohort of 95 cases of frontotemporal lobar degeneration classified according to contemporary neuropathological criteria. Forty-eight cases (51%) had TDP-43 pathology, 42 (44%) had tau pathology and five (5%) had fused-in-sarcoma pathology. Certain relatively specific clinicopathological associations were identified. Semantic dementia was predominantly associated with TDP-43 type C pathology; frontotemporal dementia and motoneuron disease with TDP-43 type B pathology; young-onset behavioural variant frontotemporal dementia with FUS pathology; and the progressive supranuclear palsy syndrome with progressive supranuclear palsy pathology. Progressive non-fluent aphasia was most commonly associated with tau pathology. However, the most common clinical syndrome (behavioural variant frontotemporal dementia) was pathologically heterogeneous; while pathologically proven Pick's disease and corticobasal degeneration were clinically heterogeneous, and TDP-43 type A pathology was associated with similar clinical features in cases with and without progranulin mutations. Volumetric magnetic resonance imaging, voxel-based morphometry and cluster analyses of the pathological groups here suggested a neuroanatomical framework underpinning this clinical and pathological diversity. Frontotemporal lobar degeneration-associated pathologies segregated based on their cerebral atrophy profiles, according to the following scheme: asymmetric, relatively localized (predominantly temporal lobe) atrophy (TDP-43 type C); relatively symmetric, relatively localized (predominantly temporal lobe) atrophy (microtubule-associated protein tau mutations); strongly asymmetric, distributed atrophy (Pick's disease); relatively symmetric, predominantly extratemporal atrophy (corticobasal degeneration, fused-in-sarcoma pathology). TDP-43 type A pathology was associated with substantial individual variation; however, within this group progranulin mutations were associated with strongly asymmetric, distributed hemispheric atrophy. We interpret the findings in terms of emerging network models of neurodegenerative disease: the neuroanatomical specificity of particular frontotemporal lobar degeneration pathologies may depend on an interaction of disease-specific and network-specific factors

Quantifying antibiotics and their metabolites in the environment via UPLC-MS/MS

Antimicrobial resistance (AMR) is a major global topic, concerning the increasing pathogenic tolerance to antibiotics. Antibiotics are becoming less effective over time as microbes develop resistance to their mechanisms of attack. This effect can be accelerated by factors such as inappropriate usage, extensive agricultural use, or long-term exposure to sub-therapeutic concentrations. Therefore, it is important to understand how antibiotics are being prescribed and used within different communities, and how they behave once introduced into the environment

The susceptibility of helicobacter pylori to the rifamycin, rifaximin

Forty strains of Helicobacter pylori had an MIC50 of 4 mg/L of the non-absorbably antibiotic, rifaximin. Neither synergy nor antagonism was demonstrated when the drug was combined with ampicillin, metronidazole and omeprazole and the rate of spontaneous mutation was less than 1 in 102. With these in-vitro characteristics, rifaximin should now be assessed for clinical efficacy. © 1995 The British Society for Antimicrobial Chemotherapy

Quantifying community-wide antimicrobials usage via wastewater-based epidemiology

Increasing usage of antimicrobials is a significant contributor to the emergence and dissemination of antimicrobial resistance. Wastewater-based epidemiology is a useful tool for evaluating public health, via the monitoring of chemical and biological markers in wastewater influent, such as antibiotics. Chemical analyses are used to determine sampled drug concentrations; measured daily flows then enable quantitation of analyte mass/day; and population estimates are utilised to calculate mass/day/1000inhabitants. These data allow for effective evaluations of drug presence and temporal trends, but do not fully represent the total quantity of drugs being consumed, i.e., human intake. Factors such as drug metabolism and physiochemical stability significantly decrease the quantity of parent drug that reaches wastewater treatment plants, leading to potential underestimations of community usage. A case study of 16 antimicrobials, and their metabolites was conducted in this study: including sulfonamides, trimethoprim, metronidazole, quinolones, nitrofurantoin, cyclines, and antiretrovirals. Correction factors (CFs) for human drug excretion, for various metabolite forms, were determined via a systematic literature review of pharmacokinetic research. Analyte stability was examined over a 24 h study. The estimation of community-wide drug intake was evaluated using the associated catchment prescription data. Overall, antimicrobials excreted in an unchanged form were often observed to over-estimate daily intake. This could be attributed to biotransformation, e.g., via glucuronide cleavage, or direct disposal of unused drugs. Acetyl-sulfonamides, trimethoprim, hydroxy-metronidazole, clarithromycin, ciprofloxacin, ofloxacin, tetracycline, and oxytetracycline generally performed well in the estimation of drug intake, relative to prescription records. The low prevalence of quinolone and trimethoprim metabolites, and the low stability of nitrofurantoin, limited the ability to evaluate these metabolites and their respective CFs. CFs established in the systematic literature review could not be validated for some metabolites in the case study due to lack of available prescription data (lamivudine, emtricitabine); an inability to quantify biomarkers (nitrofurantoin, doxycycline); being excreted at too low levels (hydroxy-trimethoprim, ofloxacin-N-oxide, desethylene-ciprofloxacin); or insufficient pharmacokinetic literature sources (the nitrofurantoin metabolite, NPAHD). Further work is currently underway to apply established CFs in other catchment with higher prevalence of antimicrobials usage